Showing papers by "St. Jude Children's Research Hospital published in 1977"

Accumulation of Hypothiocyanite Ion during Peroxidase-Catalyzed Oxidation of Thiocyanate Ion

Abstract: An oxidized form of thiocyanate accumulated during incubation of lactoperoxidase or myeloperoxidase with thiocyanate ion and low concentrations of peroxide. Addition of one mole of peroxide resulted in loss of one mole of thiocyanate and formation of one mole of the oxidation product. The oxidation product reacted with two moles of sulfhydryl to yield one mole of disulfide and one mole of thiocyanate. The same product was obtained by alkaline hydrolysis of thiocyanogen. The product is proposed to be hypothiocyanite ion. The peroxidases may catalyze the oxidation of thiocyanate to hypothiocyanite, or to thiocyanogen. Hypothiocyanite may be the antimicrobial agent formed during peroxidase-catalyzed oxidation of thiocyanate. Hypothiocyanite decomposed slowly with a second-order rate constant of 0.1 M−1 s−1 at 25°C. When the amount of peroxide added approached the amount of thiocyanate, the yield of hypothiocyanite reached a maximum and then declined. This result suggested that hypothiocyanite was oxidized by excess peroxide. Efforts to produce high concentrations of hypothiocyanite were unsuccessful, even when thiocyanate was well in excess of peroxide. As the hypothiocyanite concentration approached 0.5 mM, decomposition was accelerated and small amounts of cyanide were produced. Hypothiocyanite reacted stoichiometrically with cyanide to give products that did not oxidize sulfhydryls. Hydrolysis of thiocyanogen at neutral pH also resulted in rapid decomposition and formation of cyanide.

Persistence of Hong Kong influenza virus variants in pigs

Abstract: The A/Hong Kong/1/68 (H3N2) influenza virus which has not been isolated from man for several years, was recently isolated from pigs in Hong Kong. Influenza viruses similar to A/Victoria/3/75, which are currently circulating in man, were also isolated from pigs. Both above-mentioned viruses could be transmitted readily from pig to pig in experimental studies. The isolation of influenza viruses similar to A/Hong Kong/68 from pigs in 1976 suggests that pigs may serve as a potential reservoir for future human pandemics as well as a possible source of genetic information for recombination between human and porcine strains of influenza virus.

Propagation of Pneumocystis carinii in vitro.

Abstract: Summary: Pneumocystis carinii was propagated in vitro with primary embryonic chick epithelial lung (CEL) cells. Viability and growth of the organism were demonstrated by direct observation of the reproductive cycle in the Sykes-Moore chamber, serial passage with an increase in the number of mature cyst forms, the cytopathic effect of the organism on cell culture, and inhibition of growth of the organism by specific antiserum and pentamidine isethionate. Attempts to culture P. carinii indefinitely were not successful. However, cyst forms derived from murine and human sources increased 100-fold and 10-fold, respectively, during CEL cell culture passages. Serial passage of trophozoites alone resulted in the development of typical CPE and a maximum number of 2.8 103 cyst forms. Autoradiographic methods demonstrated active DNA, RNA, and protein synthesis within the cyst and suggest that metabolic interaction between the host cells and the organisms occurred. The nature of the attachment of P. carinii to the host CEL cell was clearly discernible by scanning electron microscopy (SEM). In the reproductive cycle a vegetative cell (designated “trophozoite”) attached by tubular expansions to the host CEL cell, probably for the transport of essential nutrients, and then detached without entering the cell. Sporozoites developed within the detached young cyst, reaching a maximum number of eight within the mature cyst. Excystment occurred through single or multiple sites in the cyst wall, after which the released trophozoite attached to a new host cell. Speculation: The in vitro propagation of P. carinii provides a basis for further studies to characterize the biologic and biochemical features of this organism and a source of antigen for the development of serologie tests for specific antibody by which the epidemiology and spectrum of clinical disease can be delineated more clearly.

Influenza in children and young adults with cancer: 20 cases.

Abstract: The purpose of this study was to characterize the clinical features of laboratory-confirmed influenza in 20 children and young adults with cancer who were receiving immunosuppressive therapy. Viruses isolated from pharyngeal and nasopharyngeal cultures were identified as the A/Hong Kong/1/68 strain or one of its variants, either A/England/42/72, A/Port Chalmers/1/73, or A/Victoria/3/75. Although the signs and symptoms of influenza in our patients were not unusual, the clinical course lasted twice as long as in the general population. Complications developed in only 3 patients and were related to secondary bacterial infections rather than influenza. An important sequelae of influenza was the interruption of cancer therapy in 16 patients for periods of 4 days to 3 1/2 weeks. The severity of influenza did not appear related to type or activity of malignancy or to duration or specific form of cancer therapy. Guidelines for the prevention and management of influenza in children with cancer are recommended.

Macromolecular Synthesis in Cells Infected by Frog Virus 3. VII. Transcriptional and Post-Transcriptional Regulation of Virus Gene Expression

Abstract: We have used improved techniques for separating individual species of RNA and protein to study the mechanisms that control gene expression by frog virus 3, a eucaryotic DNA virus. Forty-seven species of viral RNA and 35 viral polypeptide species were resolved by polyacrylamide gel electrophoresis. The relative molar ratios of virus-specific polypeptides synthesized at various times after infection were determined by computer planimetry and were compared with the molar ratios of appropriate-sized viral RNAs to code for each polypeptide. Viral polypeptides were classified according to the time during the growth cycle at which their maximal rate of synthesis occurred - early, 2 to 2.5 h; intermediate, 4 to 4.5 h; and late, 6 to 6.5 h. The viral RNAs, which were assumed to be mRNA's, could not be classified according to time of maximum synthesis; once their synthesis had begun, most of the RNAs continued to be synthesized at the same or higher rates. However, only 10 of the 47 viral RNA bands were plainly visible after electrophoresis of extracts from cells labeled from 1 to 1.5 h after infection; these 10 RNAs were designated "early" RNA. The early pattern of both RNA and polypeptide synthesis was maintained for at least 6 h in the presence of the amino acid analog fluorophenylalanine, which indicates that a functional viral polypeptide was required for "late" transcription and translation. The presumptive mRNA's for late polypeptides did not appear until 2 h after infection, but two of these "late" RNAs became the major products of transcription by 4 h into the infectious cycle. In contrast to the declining rate of synthesis of the early proteins, corresponding early RNA species continued to be synthesized at the same or higher rates throughout the replicative cycle. Although the synthesis of late virus-specific proteins appeared to be regulated at the level of transcription, our results suggest that the synthesis of both early and intermediate proteins was regulated at the post-transcriptional level.

Colorectal carcinoma in adolescents implications regarding etiology.

Abstract: Between October, 1974 and December, 1976, 13 adolescent patients with far-advanced, poorly differentiated colorectal carcinoma had been referred to a pediatric cancer center. All patients received chemotherapy with vincristine, methyl-CCNU and 5-fluorouracil. Five of 13 patients are living, one of whom remains disease-free after 12 months of chemotherapy. Four of the patients were from urban areas and nine from rural areas. One of four from urban areas had intimate exposure to chemicals used in the production of cotton and soy beans. Eight of nine patients from rural areas also had exposure to farm or agricultural chemicals, and three of these patients were intimately involved with the spraying operations. Suggestions regarding etiology and causative factors for the development of carcinoma of the colon in adults have previously been advanced. Results of these studies suggest that alternate etiologies must be suggested for adolescent colorectal carcinoma.

Adjuvant multiple drug chemotherapy for osteosarcoma of the extremity

Abstract: Results of treatment for osteosarcoma of the extremity have been poor with metastases usually causing death within 2 years following diagnosis. Because of the great risk of development of metastases, 20 patients have received adjuvant chemotherapy with Adriamycin, cyclophosphamide and high-dose methotrexate-leucovorin rescue for up to 12 months following amputation for osteosarcoma. Sixteen of these patients are surviving; 11 are free of evident tumor from 6 to 34 months following amputation. Five patients were found to have pulmonary metastases while receiving chemotherapy and three patients developed metastases following completion of chemotherapy. One patient died following her third treatment with high-dose methotrexate-leucorovin rescue. Other toxicity included nausea, vomiting, mucosal ulcerations, infections, hematologic abnormalities, changes in kidney and liver functions tests, and minor coagulation abnormalities. The natural history of osteosarcoma may have been modified by the use of these agents for periods exceeding the median time to predicted detection of pulmonary metastases. Microscopic metastases of some patients were eradicated by this adjuvant chemotherapy. For patients who developed metastases, these metastases were delayed in their time of detection and in their number at the time of detection.

Methotrexate-induced sudden fatal pulmonary reaction.

Abstract: A teenage girl in bone marrow remission with acute lymphocytic leukemia died suddenly from pulmonary edema. She had taken her first oral dose of methotrexate and cyclophosphamide 10 hours previously when she was feeling well and was asymptomatic. One week previously she had received the last of four intrathecal injections of methotrexate. Autopsy showed marked pulmonary edema as well as chronic lung changes, as previously described in patients with methotrexate pneumonitis. There is usually at least a 12-day interval from the onset of administration of methotrexate to the onset of the lung toxicity. The authors suggest the patient was sensitized by the intrathecal methotrexate and then reacted with angioneurotic edema of the lung when given the first oral dose of methotrexate. Careful examination for infectious agents, including electron microscopy, was negative.

Biphasic Thrombopoietic Response to Severe Hypobaric Hypoxia

Abstract: Thrombopoiesis has been studied during and after an 11 d exposure to discontinuous hypobaric hypoxia. Exposure of rats to 0.4 atmospheres for 16--17 h daily initially caused an increase in platelet count which reached a peak of 1.5 times baseline on days 4 and 5. This thrombocytosis was followed by a decrease in platelets to a nadir of 50--60% of baseline on days 12 and 13. That thrombocytosis results from increased platelet production is supported by increased [35S]sulphate incorporation into platelets and increased megakaryocyte size and turnover. The thrombocytopenia with continued hypoxia seems to result from decreased platelet production since 51Cr-platelet survival was normal while megakaryocyte concentration was decreased to one-half that of untreated controls. These observations suggest that differentiation of precursors into megakaryocytes was decreased during the thrombocytopenic period, although the fewer remaining megakaryocytes appeared stimulated because of their larger size and increased [3H]thymidine labelling. Thus, hypobaric hypoxia had a biphasic effect on thrombopoiesis with increased platelet production in the first few days of exposure followed by subnormal production.

Lead poisoning from ingestion of Chinese herbal medicine.

Abstract: A 4-month-old infant was proven to have acute plumbism attributed to the ingestion of lead-containing Chinese herbal medicines. The analyses of 11 brands of Chinese herbal medicines by flameless atomic absorption spectrophotometry revealed that one of the medicines, Po Ying Tan, made by company A, had a mean lead content of 7.5 mg per unit dose; the other 10 brands had lower but still significant lead contents. In Chinese communities, these medicines are used very frequently, without prescription, for many minor ailments. This practice places a large number of individuals at risk for acute and chronic lead poisoning. Language: en

Relative utilization of fatty acids for synthesis of ketone bodies and complex lipids in the liver of developing rats.

Abstract: The regulation of hepatic ketogenesis, as related to the metabolism of fatty acids through oxidative and synthetic pathways, was studied in developing rats. [1-14C] palmitate was used as a substrate to determine the proportions of free fatty acids utilized for the production of ketone bodies, CO2 and complex lipids. Similar developmental patterns of hepatic ketogenesis were obtained by measuring the production of either [14C]acetoacetate from exogenous [1-14C] palmitate or the sum of unlabeled acetoacetate and β-hydroxybutyrate from endogenous fatty acids. The production of total ketone bodies was low during the late fetal stage and at birth, but increased rapidly to a maximum value within 24 hr after birth. The maximal ketogenic capacity appeared to be maintained for the first 10 days of life.14CO2 production from [1-14C] palmitate increased by two- to fourfold during the suckling period, from its initial low rate seen at birth. The capacity for synthesis of total complex lipids was low at birth and had increased by day 3 to a maximal value, which was comparable to that of adult fed rats. The high lipogenic capacity lasted throughout the remaining suckling period. When ketogenesis was inhibited by 4-pentenoic acid, the rate of synthesis of complex lipids did not increase despite an increase in unutilized fatty acids. During the mid-suckling period, approximately equal amounts of [1-14C] palmitate were utilized for the synthesis of ketone plus CO2 and for complex lipid synthesis. By contrast, in adult fed rats, the incorporation of fatty acids into complex lipids was four times higher than that of ketone plus CO2. These observations suggest that stimulated hepatic ketogenesis in suckling rats results from the rapid oxidation of fatty acids and consequent increased production of acetyl CoA, but not from impaired capacity for synthsis of complex lipids.

Evidence that Stimulation of Megakaryocytopoiesis by Low Dose Vincristine Results from an Effect on Platelets

Abstract: Appropriate low dosages of vincristine stimulate megakaryocytopoiesis and produce thrombocytosis. In this study of the thrombocytotic action of vincristine, administration of a single dose of 0.1 mg/kg to rats produced an increase in megakaryocyte concentration, diameter and 24 h [3H]thymidine labelling index. Transfusion of one body equivalent of platelets from normal donors prevented stimulation of megakaryocytopoiesis by vincristine whereas platelets from vincristine-treated donors did not. These results suggest that vincristine stimulates megakaryocytopoiesis by altering the functional role of circulating platelets in the regulation of thrombopoiesis.

Radiotherapy in leukemia and lymphoma of children.

Abstract: Radiotherapy is important in the treatment of leukemia and lymphoma of children. In acute lymphocytic leukemia administration of cranial irradiation early during chemotherapy-induced remission prevents initial meningeal relapse. When cranial irradiation is combined with a 3-year course of multiple drug systemic chemotherapy approximately one-half of the children remain in complete remission for 5 years or more and are at little risk of relapse. Preventive cranial irradiation is effective in children with acute myelocytic leukemia, also, but this does not affect survival because of the inadequacy of chemotherapy in controlling bone marrow disease. Low dose palliative irradiation can be helpful in caring for some children with obstructive, painful or disabling leukemic lesions. In Hodgkin's disease of children radiotherapy is effective in curing stages IA, IIA, and IIIA disease and contributes to chemotherapy control of stages IIIB and IV disease. The role of radiotherapy in non-Hodgkin's lymphoma is less clear. Children with T-lymphoblastic lymphoma tend to have rapid dissemination to bone marrow and meninges and appear to benefit more from multiple agent chemotherapy and preventive meningeal irradiation. Children with B-lymphoblastic lymphoma usually benefit from cyclophosphamide therapy; the value of irradiation is yet to be established. However, radiotherapy is frequently curative in stage I B-lymphocytic nodular and histiocytic lymphomas. The indications for radiotherapy in children with leukemia and lymphoma are constantly changing. Before each child is treated the multi disciplinary evaluation and treatment team must consider the rationale in relation to the specific child and current knowledge.

Isolation of an influenza virus, similar to A/Port Chalmers/1/73 (H3N2) from a common murre at Sakhalin Island in U.S.S.R (Strain A/CommonMurre/Sakhalin/1/74)

Abstract: An influenza A virus isolated from the cloaca of a common murre was characterized antigenically as H3N2 and was most closely related to the A/Port Chalmers/1/73 strain. Serological studies of sera collected from common murres in the area of virus isolation showed that 21 per cent of the birds had antibodies to Hong Kong influenza virus.

Cell differentiation antigens versus tumor-related antigens in childhood acute lymphoblastic leukemia (ALL). Clinical significance of leukemia markers.

Abstract: Acute lymphocytic leukemia is the most common malignancy of childhood. In spite of recent advances in treatment, about half of children with ALL become refractory to treatment. A current challenge is to define the differences between poor and good re-ponders and to develop different modalities of treatment for children with a high risk for relapse. In order to understand the interactions between tumor and host cells that might influence these differential responses we have concentrated our investigations on the cell surface characteristics of bone marrow lymphoblasts from children with ALL.

Osteosarcoma in 2 very young children.

Abstract: sarcoma. A craniotomy removed all visible tumor. The postoperative course was unremarkable. The patient was then referred to our institution. On physical examination there were no unusual features other than minimal left proptosis and a healed surgical scar. Laboratory data were normal except for the bone scan, which showed increased uptake in the region of the left orbit. Review of the specimen confirmed the existence of osteo-

Childhood rhabdomyosarcoma of the extremity: results of combined modality therapy.

Abstract: Fifteen children with rhabdomyosarcoma of an extremity were treated with one of several combinations of surgery, radiotherapy, and chemotherapy, depending on stage of disease at diagnosis. All patients received combination chemotherapy administered as a 4‐ to 6‐week induction course, followed by 12 to 18 months of continuation chemotherapy. When feasible, the primary tumor was resected en bloc before chemotherapy was begun. Following the induction regimen, patients with either unresectable regional tumor, or disseminated tumor and an initial complete response to chemotherapy, received megavoltage radiotherapy to the primary site and regional lymphatics. Eleven of 15 patients (0.73) developed or maintained a complete tumor response to induction therapy alone. Radiotherapy maintained control of local disease in six of six patients treated. Overall, six patients, including one with disseminated disease at diagnosis, are surviving 15 to 45 months from diagnosis; four have been clinically free of tumor for more than 36 months. The presence or absence of dissemination at diagnosis and location of primary tumor on the extremity were significant determinants of survival (p < .01). Antecedent trauma to the primary site resulted in delay in diagnosis in five patients but did not directly affect survival. Documented bone marrow infiltration during the clinical course was associated with either cardiac or intracranial tumor or both in five of six evaluable patients. Primary involvement of an extremity by rhabdomyosarcoma has been reported to have an unfavorable influence upon survival compared with involvement of nonextremity sites. The combined results of the current study and more recent prospective controlled series fail to support these earlier studies and demonstrate that any prognostic significance of anatomic site is lost, when analyzed by stage. Cancer 40:2810‐2816, 1977.

Characterization of human enzymes specific for damaged DNA: resolution of endonuclease for irradiated DNA from an apparent N-glycosidase active on alkylated DNA

Abstract: An endonuclease partially purified from human lymphoblasts, and active against ultraviolet-irradiated DNA, was found to act additionally on DNA damaged by either x-radiation or methylmethanesulfonate. To determine if these activities were truly endonucleolytic, the reaction products were analyzed under conditions that prevented conversion of apurinic or apyrimidinic sites to single-strand breaks. With either ultraviolet- or x-irradiated DNA, strand breakage remained maximal, hence confirming the endonucleolytic character of the enzyme. By contrast, with DNA alkylated with methylmethanesulfonate, strand breakage was sharply reduced. Additional experiments indicated that the activity for alkylated DNA induces strand breaks only in concert with a purified endonuclease specific for apurinic sites, suggesting that it is an N-glycosidase that depurinates alkylated bases. This enzyme was separated from the endonuclease specific for irradiated DNA, by chromatography on DNA-agarose.